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Melanoma investigations point to new drug

Melanoma is the third most common cancer in Australian men and women – and a wily opponent for researchers like the Olivia Newton-John Cancer Research Institute’s Dr Erinna Lee.

Significant advances have been made into treating melanoma but unfortunately not all patients respond to the treatments available. Erinna and her colleagues are making inroads into finding new drugs to help these patients.

The researchers are tackling a family of proteins implicated in melanoma, called BCL-2, which act to keep the cancers alive. BCL-2 proteins are essential for determining the survival of all cells but when this process goes awry they can also contribute to the development of cancer.

“We’re starting to realise that melanoma may in fact be clever enough to escape chemotherapy-induced cell death by relying on a larger repertoire of pro-survival BCL-2 proteins for survival,” says Erinna.

“Our research in vitro and in animal models has recently shown that a more robust combination of drugs might be required. We are now looking at different combinations of drugs that will be able to kill melanoma more aggressively,” she says.

The researchers, working in the Cell Death and Survival Laboratory, have developed novel compounds that can specifically target certain BCL-2 family members and neutralise their pro-survival activity in cells.

Drug combinations the key to killing melanoma

The scientists have used the compounds to show that the inactivation of two proteins – called MCL-1 and BFL-1 – kills melanoma cells relatively well. A new drug acting against MCL-1 has been developed elsewhere but there is still no drug available against BFL-1.

Erinna says that based on current results, the researchers now believe that a drug targeting BFL-1 could be highly effective for treatment of melanoma, particularly if used in combination with the currently available MCL-1-targeting molecule.

Approach may work with other cancers

The researchers will use their findings to focus on developing drugs in the future that work against BCL-2 proteins for potential treatments.

Additionally, the compound they have developed allows them to profile other cancer types and see if they are dependent on BFL-1 for their survival. The scientists hope that using this approach could identify other cancer patients for which a BFL-1-specific drug could be useful if, and when, it is developed.

Some of the work involved researchers at the Walter Eliza Hall Institute. More findings are expected in late 2017 or early 2018.

Dr Erinna Lee is a Postdoctoral research fellow in the Cell Death and Survival Laboratory. Read more about their work.